Jhingook Kim

Chung SR, et al. Korean J Thorac Cardiovasc Surg. 2012 Aug;45(4):267-268. http://dx.doi.org/10.5090/kjtcs.2012.45.4.267

Thymic epithelial tumours (TETs), the most common tumour of the anterior mediastinum, are epithelial neoplasms of the thymus with a wide spectrum of morphologic features. We retrospectively analysed clinical features of TET and the correlation of World Health Organisation (WHO) histologic classification and Masaoka staging system with different treatment modalities in 195 patients, from 1995 to 2005. According to the Masaoka's staging system, there were 78 (40.0 %) patients with stage I, 38 (19.5%) with stage II, 41 (21.0%) with stage III, 38 (19.5%) with stage IV. All patients were reclassified according to the WHO criteria as follows: Type A (n=9, 4.6%), AB (n=37, 18.9%), B1 (n=29, 14.8%), B2 (n=48, 24.6%), B3 (n=40, 20.5%), C (n=32, 16.4%). There was a fairly good correlation between Masaoka staging and WHO histotype (PPPn=57) had more favourable disease-free and overall survival as compared with those without adjuvant treatment (n=20) (P=0.015, 0.015, respectively). Given that the predominant sites of recurrence after surgery was pleura/pericardium and lung, and the fact that complete resection was a significant influential factor for survival at log–rank test, an active investigation of newer treatment strategies such as neoadjuvant treatment to improve the resectability and development of optimal adjuvant treatment modality is a high priority especially for those with high-risk for recurrence or in patients with advanced stage disease.

Background and Objectives We wanted to assess whether the level of enzyme activity for a particular matrix metalloproteinase (MMP), and not the amount of expressed protein, in lung tissue could be used as a reliable prognostic biomarker for tumor recurrence leading to poorer survival in a certain subgroup of patients who have undergone curative resection for stage I human NSCLC. Methods We determined what type of MMP was significant for tumor recurrence by using a mouse model of pulmonary metastasis with inoculating the footpad with H460 human cancer cells. We then looked for any association between tumor recurrence and the level of enzyme activities for the selected MMP in the tumor and also in the pathologically non‐tumorous tissues from 34 stage I lung cancer patients. Results We obtained H460/PM6 cells having a highly metastatic potential after six repeated cycles of pulmonary metastasis by using the mouse footpad inoculated with the metastasized cancer cells in the previous cycle. We started with human lung cancer cells, H460, and we found that among the tested MMPs we tested for, the level of MMP‐2 mRNA was elevated. No significant difference was seen in the level of enzyme activity of the MMP‐2 cells from the curatively resected tumor tissues of the stage I NSCLC patients who were later found with or without recurrence. However, the level of MMP‐2 enzyme activity was found to be significantly different between the non‐tumorous lung tissues from patients later found with and without recurrence, and it was associated with the 5‐year survival rate. Conclusions This observation suggests that the higher level of MMP‐2 enzyme activity in the non‐tumorous tissues from the patients could be used as a prognostic biomarker to predict post‐operative tumor recurrence and survival for patients with stage I NSCLC. The elevated enzyme activity of MMP‐2 in the non‐tumorous tissue resected from stage I NSCLC could be used as a prognostic indicator for post‐operative tumor recurrence and the patients' poor survival. Further, this could be an important aid for physicians' making decision on whether to subject particular patients to post‐operative adjunct chemotherapy. J. Surg. Oncol. 2007;95:337–346.

I H, et al. J Korean Med Sci. 2006 Apr;21(2):236-241. http://dx.doi.org/10.3346/jkms.2006.21.2.236

Chang JW, et al. J Korean Med Sci. 2006 Dec;21(6):1017-1020. http://dx.doi.org/10.3346/jkms.2006.21.6.1017

Kim HS, et al. J Korean Med Sci. 2006 Apr;21(2):224-228. http://dx.doi.org/10.3346/jkms.2006.21.2.224

Aberrant methylation of several tumor suppressor genes often occurs during the pathogenesis of lung cancer. RASSF1A is one of the tumor suppressor genes, and it is frequently inactivated by hypermethylation of its promoter region in a variety of human cancers, including lung cancer. It has recently been suggested that RASSF1A methylation was frequently observed in poorly differentiated tumors, and that it was correlated with adverse survival in lung adenocarcinoma (Tomizawa Y, et al., Clin Cancer Res 2002;8:2362-8). In this study, we investigated the pathogenetic and clinicopathologic significance of RASSF1A methylation for the development and/or progression of non small cell lung cancer (NSCLC). We examined 116 cases of NSCLC for the methylation status of RASSF1A. Methylation-specific analysis demonstrated that 40.5% (47 of 116) of the cases were methylated at the CpG sites in the promoter. Methylation of RASSF1A was associated with cellular differentiation (p = 0.0244) and it was related to survival (p = 0.0276). However, there was no association between RASSF1A methylation and the individual clinicopathologic features: TNM stage (p > 0.1), recurrence (p > 0.1), lymphatic permeation (p > 0.1) and smoking duration time (p > 0.1). Furthermore, we analyzed RASSF1A's probability as a prognostic marker by using stepwise Cox proportional hazard regression testing. As a result, the stage proved to be the most important factor (p = 0.0089), more than any other factors such as age, gender, cell type, methylation status, differentiation, smoking duration time, tumor size and lymph node permeation. There was no other significant factor other than stage and age. These results show that epigenetic inactivation of RASSF1A cannot be a prognostic marker of NSCLC.

The aim of the present study was to evaluate the pattern of recurrence after complete resection of pathological stage I, II non-small cell lung cancer, especially according to the cell type. We reviewed the clinical records of 525 patients operated on for pathologic stage I and II lung cancer. The histologic type was found to be squamous in 253 and non-squamous in 229 patients. Median follow-up period was 40 months. Recurrences were identified in 173 (36%) of 482 enrolled patients; distant metastasis in 70%, distant and local recurrence in 11%, and local recurrence in 19%. Distant metastasis was more common in non-squamous than in squamous cell carcinoma (p=0.044). Brain metastasis was more frequently identified in non-squamous than in squamous cell carcinoma (24.2% vs. 7.3%. p=0.005). Multivariate analyses showed that cell type is the significant risk factor for recurrence-free survival in stage I and stage II non-small cell lung cancer. Recurrence-free survival curves showed that non-squamous cell carcinoma had similar risks during early periods of follow-up and more risks after 2 yr from the operation compared to squamous cell carcinoma. Pathological stage and histologic type significantly influence recurrence-free survival.